ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2001
Neuronal Ca(V)1.3alpha(1) L-type channels activate at relatively hyperpolarized membrane potentials and are incompletely inhibited by dihydropyridines.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 293 papers.
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Who cites it
293 citing papers in PubMed, 512 citations in OpenAlex.
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233 more citing papers are in PubMed but not listed here.
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
Abstract
L-type calcium channels regulate a diverse array of cellular functions within excitable cells. Of the four molecularly defined subclasses of L-type Ca channels, two are expressed ubiquitously in the mammalian nervous system (Ca(V)1.2alpha(1) and Ca(V)1.3alpha(1)). Despite diversity at the molecular level, neuronal L-type channels are generally assumed to be functionally and pharmacologically similar, i.e., high-voltage activated and highly sensitive to dihydropyridines. We now show that Ca(V)1.3alpha(1) L-type channels activate at membrane potentials approximately 25 mV more hyperpolarized, compared with Ca(V)1.2alpha(1). This unusually negative activation threshold for Ca(V)1.3alpha(1) channels is independent of the specific auxiliary subunits coexpressed, of alternative splicing in domains I-II, IVS3-IVS4, and the C terminus, and of the expression system. The use of high concentrations of extracellular divalent cations has possibly obscured the unique voltage-dependent properties of Ca(V)1.3alpha(1) in certain previous studies. We also demonstrate that Ca(V)1.3alpha(1) channels are pharmacologically distinct from Ca(V)1.2alpha(1). The IC(50) for nimodipine block of Ca(V)1.3alpha(1) L-type calcium channel currents is 2.7 +/- 0.3 microm, a value 20-fold higher than the concentration required to block Ca(V)1.2alpha(1). The relatively low sensitivity of the Ca(V)1.3alpha(1) subunit to inhibition by dihydropyridine is unaffected by alternative splicing in the IVS3-IVS4 linker. Our results suggest that functional and pharmacological criteria used commonly to distinguish among different Ca currents greatly underestimate the biological importance of L-type channels in cells expressing Ca(v)1.3alpha(1).
Indexed as
Identifiers
11487617PMC6763157W1641622793What OpenQuestion holds
Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.